Back to resultsSafety and Efficacy of Entospletinib With Vincristine and Dexamethasone in Adults With Relapsed or Refractory Acute Lymphoblastic Leukemia (ALL)
Primary Purpose
Acute Lymphoblastic Leukemia
Status
Terminated
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Entospletinib
Vincristine
Dexamethasone
CNS Prophylaxis
Sponsored by
About this trial
This is an interventional treatment trial for Acute Lymphoblastic Leukemia focused on measuring Syk inhibitor, Blood malignancy, Leukemia
Eligibility Criteria
Key Inclusion Criteria:
- Adults with ALL in need of treatment
Key Exclusion Criteria:
- Diagnosis of Burkitt's Leukemia, or lymphoid blast crisis of chronic myelogenous leukemia (CML)
- History of myelodysplastic syndrome or solid organ transplantation
- Prior allogeneic bone marrow progenitor cell transplant within 100 days or on active immunosuppression for graft versus host disease (GVHD) treatment or prophylaxis within 28 days prior to enrollment
Note: Other protocol defined Inclusion/ Exclusion criteria may apply.
Sites / Locations
- City of Hope
- UCLA
- UC Irvine Medical Center
- University of California San Diego (UCSD)
- University of Chicago
- Hackensack University Medical Center
- Memorial Sloan-Kettering
- The Ohio State University
- Bon Secour St. Francis Hospital
- University of WA
- Princess Margaret
- Medizinische Klinik mit Schwerpunkt Hepatologie & Gastroenterology
- Medizinische Klinik und Poliklinik I
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Experimental
Experimental
Experimental
Arm Label
ENTO 200 mg + VCR 0.5 mg
ENTO 400 mg + VCR 0.5 mg
ENTO 400 mg + VCR 1.0 mg
ENTO 400 mg + VCR 2.0 mg
Arm Description
Monotherapy Lead-In (Day -7 to Day -1): Entospletinib (ENTO) 200 mg tablet orally twice daily as a single agent. Induction (two 28-day cycles): ENTO 200 mg twice daily continuously in combination with vincristine (VCR) 0.5 mg intravenously (IV) on Days 1, 8, 15, and 22 of each cycle; dexamethasone (DEX) 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and central nervous system (CNS) prophylaxis per institutional standards on Day 28 of each cycle. Maintenance (up to 36, 28-day cycles): Participants who achieved a complete remission (CR) received stem cell transplant (SCT) (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a partial response [PR]) after induction were offered maintenance therapy with ENTO 200 mg twice daily continuously in combination with VCR 0.5 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.
Monotherapy Lead-In (Day -7 to Day -1): ENTO 400 mg tablet orally twice daily as a single agent. Induction (two 28-day cycles): ENTO 400 mg twice daily continuously in combination with VCR 0.5 mg IV on Days 1, 8, 15, and 22 of each cycle; DEX 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and CNS prophylaxis per institutional standards on Day 28 of each cycle. Maintenance (up to 36, 28-day cycles): Participants who achieved a CR received SCT (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a PR) after induction were offered maintenance therapy with ENTO 400 mg twice daily continuously in combination with VCR 0.5 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.
Monotherapy Lead-In (Day -7 to Day -1): ENTO 400 mg tablet orally twice daily as a single agent. Induction (two 28-day cycles): ENTO 400 mg twice daily continuously in combination with VCR 1.0 mg IV on Days 1, 8, 15, and 22 of each cycle; DEX 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and CNS prophylaxis per institutional standards on Day 28 of each cycle. Maintenance (up to 36, 28-day cycles): Participants who achieved a CR received SCT (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a PR) after induction were offered maintenance therapy with ENTO 400 mg twice daily continuously in combination with VCR 1.0 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.
Monotherapy Lead-In (Day -7 to Day -1): ENTO 400 mg tablet orally twice daily as a single agent. Induction (two 28-day cycles): ENTO 400 mg twice daily continuously in combination with VCR 2.0 mg IV on Days 1, 8, 15, and 22 of each cycle; DEX 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and CNS prophylaxis per institutional standards on Day 28 of each cycle. Maintenance (up to 36, 28-day cycles): Participants who achieved a CR received SCT (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a PR) after induction were offered maintenance therapy with ENTO 400 mg twice daily continuously in combination with VCR 2.0 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.
Outcomes
Primary Outcome Measures
Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs)
The occurrence of any of the following toxicities during Lead-in/Cycle 1 (Day -7 through Day 28) was considered a DLT if judged by the investigator to be possibly, probably, or definitely related to the administration of any drug in the treatment regimen (ENTO, VCR, DEX, institutional standard CNS prophylaxis):
Grade 4 (or higher) non-hematologic toxicity
Grade 3 non-hematologic toxicity lasting ≥ 7 days despite optimal supportive care
Any Grade 3 non-hematologic laboratory value if:
Medical intervention was required to treat, or
The abnormality led to hospitalization, or
The abnormality persisted for > 1 week
Grade 4 Neutropenia (absolute neutrophil count [ANC] < 500 /μL) persistent for greater than 14 days or associated with febrile neutropenia
Grade 4 thrombocytopenia (platelets < 25,000/μL) persisting for greater than 14 days (or greater than 25,000 /μL, but requiring prophylactic platelet transfusion to maintain this level)
Secondary Outcome Measures
Percentage of Participants With Complete Remission (CR) at the End of Induction
Assessment of clinical response was made according to National Comprehensive Cancer Network (NCCN) guidelines on acute lymphoblastic leukemia (ALL) Version 2, 2016. CR required all of the following:
No circulating blasts or extramedullary disease (no lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement).
Trilineage hematopoiesis (TLH) and < 5% blasts in bone marrow aspirate.
ANC > 1000/μL.
Platelets > 100,000/μL.
Percentage of Participants With Overall Remission at the End of Induction
Assessment of clinical response was made according to NCCN guidelines on ALL Version 2, 2016. Overall remission included CR and complete remission with incomplete hematologic recovery (CRi). CR required all of the following:
No circulating blasts or extramedullary disease (no lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement).
TLH and < 5% blasts in bone marrow aspirate.
ANC > 1000/μL.
Platelets > 100,000/μL.
CRi required all criteria for CR except platelet count and/or ANC:
Platelets ≤ 100,000/μL and/or ANC is ≤ 1000/μL
Percentage of Participants With Partial Response (PR) at the End of Induction
PR required all of the following:
No circulating blasts or extramedullary disease (no lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement).
TLH and bone marrow may contain ≥ 5% but less than 25% blast morphology.
ANC > 1000/μL.
Platelets > 100,000/μL.
Percentage of Participants With Overall Response at the End of Induction
Overall response included CR, CRi, and PR. CR required all of the following:
No circulating blasts or extramedullary disease (no lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement).
TLH and < 5% blasts in bone marrow aspirate.
ANC > 1000/μL.
Platelets > 100,000/μL.
CRi required all criteria for CR except platelet count and/or ANC:
Platelets ≤ 100,000/μL and/or ANC is ≤ 1000/μL
PR required all criteria for CR except for bone marrow blasts:
bone marrow may contain ≥ 5% but less than 25% blast morphology
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02404220
Brief Title
Safety and Efficacy of Entospletinib With Vincristine and Dexamethasone in Adults With Relapsed or Refractory Acute Lymphoblastic Leukemia (ALL)
Official Title
A Phase 1b/2, Open-Label, Dose Escalation and Expansion Study Evaluating the Safety and Efficacy of Entospletinib (GS-9973) With Vincristine and Dexamethasone in Adult Subjects With Relapsed or Refractory Acute Lymphoblastic Leukemia (ALL)
Study Type
Interventional
2. Study Status
Record Verification Date
December 2019
Overall Recruitment Status
Terminated
Study Start Date
May 6, 2015 (Actual)
Primary Completion Date
November 16, 2018 (Actual)
Study Completion Date
December 17, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Gilead Sciences
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The primary objective of this study is to evaluate the safety of entospletinib in combination with vincristine (VCR), and dexamethasone (DEX) in adults with previously treated relapsed or refractory B-cell lineage acute lymphoblastic leukemia (ALL).
This is a dose escalation study in which after 2 induction cycles participants may be put on maintenance for up to 36 cycles if they have obtained clinical benefit from the treatment.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute Lymphoblastic Leukemia
Keywords
Syk inhibitor, Blood malignancy, Leukemia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
30 (Actual)
8. Arms, Groups, and Interventions
Arm Title
ENTO 200 mg + VCR 0.5 mg
Arm Type
Experimental
Arm Description
Monotherapy Lead-In (Day -7 to Day -1): Entospletinib (ENTO) 200 mg tablet orally twice daily as a single agent.
Induction (two 28-day cycles): ENTO 200 mg twice daily continuously in combination with vincristine (VCR) 0.5 mg intravenously (IV) on Days 1, 8, 15, and 22 of each cycle; dexamethasone (DEX) 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and central nervous system (CNS) prophylaxis per institutional standards on Day 28 of each cycle.
Maintenance (up to 36, 28-day cycles): Participants who achieved a complete remission (CR) received stem cell transplant (SCT) (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a partial response [PR]) after induction were offered maintenance therapy with ENTO 200 mg twice daily continuously in combination with VCR 0.5 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.
Arm Title
ENTO 400 mg + VCR 0.5 mg
Arm Type
Experimental
Arm Description
Monotherapy Lead-In (Day -7 to Day -1): ENTO 400 mg tablet orally twice daily as a single agent.
Induction (two 28-day cycles): ENTO 400 mg twice daily continuously in combination with VCR 0.5 mg IV on Days 1, 8, 15, and 22 of each cycle; DEX 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and CNS prophylaxis per institutional standards on Day 28 of each cycle.
Maintenance (up to 36, 28-day cycles): Participants who achieved a CR received SCT (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a PR) after induction were offered maintenance therapy with ENTO 400 mg twice daily continuously in combination with VCR 0.5 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.
Arm Title
ENTO 400 mg + VCR 1.0 mg
Arm Type
Experimental
Arm Description
Monotherapy Lead-In (Day -7 to Day -1): ENTO 400 mg tablet orally twice daily as a single agent.
Induction (two 28-day cycles): ENTO 400 mg twice daily continuously in combination with VCR 1.0 mg IV on Days 1, 8, 15, and 22 of each cycle; DEX 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and CNS prophylaxis per institutional standards on Day 28 of each cycle.
Maintenance (up to 36, 28-day cycles): Participants who achieved a CR received SCT (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a PR) after induction were offered maintenance therapy with ENTO 400 mg twice daily continuously in combination with VCR 1.0 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.
Arm Title
ENTO 400 mg + VCR 2.0 mg
Arm Type
Experimental
Arm Description
Monotherapy Lead-In (Day -7 to Day -1): ENTO 400 mg tablet orally twice daily as a single agent.
Induction (two 28-day cycles): ENTO 400 mg twice daily continuously in combination with VCR 2.0 mg IV on Days 1, 8, 15, and 22 of each cycle; DEX 20 mg twice daily orally on Days 8-11 and Days 22-25 (Cycle 1) and on Days 1-4 and Days 15-18 (Cycle 2); and CNS prophylaxis per institutional standards on Day 28 of each cycle.
Maintenance (up to 36, 28-day cycles): Participants who achieved a CR received SCT (if eligible) per investigator's discretion; others who obtained clinical benefit (ie, at least a PR) after induction were offered maintenance therapy with ENTO 400 mg twice daily continuously in combination with VCR 2.0 mg on Day 1 of each cycle and DEX (20 mg daily or 10 mg twice daily) on Days 1-4 and Days 15-18 of each cycle.
Intervention Type
Drug
Intervention Name(s)
Entospletinib
Other Intervention Name(s)
GS-9973, ENTO
Intervention Type
Drug
Intervention Name(s)
Vincristine
Other Intervention Name(s)
VCR
Intervention Type
Drug
Intervention Name(s)
Dexamethasone
Other Intervention Name(s)
DEX
Intervention Type
Drug
Intervention Name(s)
CNS Prophylaxis
Primary Outcome Measure Information:
Title
Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs)
Description
The occurrence of any of the following toxicities during Lead-in/Cycle 1 (Day -7 through Day 28) was considered a DLT if judged by the investigator to be possibly, probably, or definitely related to the administration of any drug in the treatment regimen (ENTO, VCR, DEX, institutional standard CNS prophylaxis):
Grade 4 (or higher) non-hematologic toxicity
Grade 3 non-hematologic toxicity lasting ≥ 7 days despite optimal supportive care
Any Grade 3 non-hematologic laboratory value if:
Medical intervention was required to treat, or
The abnormality led to hospitalization, or
The abnormality persisted for > 1 week
Grade 4 Neutropenia (absolute neutrophil count [ANC] < 500 /μL) persistent for greater than 14 days or associated with febrile neutropenia
Grade 4 thrombocytopenia (platelets < 25,000/μL) persisting for greater than 14 days (or greater than 25,000 /μL, but requiring prophylactic platelet transfusion to maintain this level)
Time Frame
ENTO Lead-in and Cycle 1 (Day -7 through Day 28)
Secondary Outcome Measure Information:
Title
Percentage of Participants With Complete Remission (CR) at the End of Induction
Description
Assessment of clinical response was made according to National Comprehensive Cancer Network (NCCN) guidelines on acute lymphoblastic leukemia (ALL) Version 2, 2016. CR required all of the following:
No circulating blasts or extramedullary disease (no lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement).
Trilineage hematopoiesis (TLH) and < 5% blasts in bone marrow aspirate.
ANC > 1000/μL.
Platelets > 100,000/μL.
Time Frame
End of Induction (Cycle 2, Day 28)
Title
Percentage of Participants With Overall Remission at the End of Induction
Description
Assessment of clinical response was made according to NCCN guidelines on ALL Version 2, 2016. Overall remission included CR and complete remission with incomplete hematologic recovery (CRi). CR required all of the following:
No circulating blasts or extramedullary disease (no lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement).
TLH and < 5% blasts in bone marrow aspirate.
ANC > 1000/μL.
Platelets > 100,000/μL.
CRi required all criteria for CR except platelet count and/or ANC:
Platelets ≤ 100,000/μL and/or ANC is ≤ 1000/μL
Time Frame
End of Induction (Cycle 2, Day 28)
Title
Percentage of Participants With Partial Response (PR) at the End of Induction
Description
PR required all of the following:
No circulating blasts or extramedullary disease (no lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement).
TLH and bone marrow may contain ≥ 5% but less than 25% blast morphology.
ANC > 1000/μL.
Platelets > 100,000/μL.
Time Frame
End of Induction (Cycle 2, Day 28)
Title
Percentage of Participants With Overall Response at the End of Induction
Description
Overall response included CR, CRi, and PR. CR required all of the following:
No circulating blasts or extramedullary disease (no lymphadenopathy, splenomegaly, skin/gum infiltration/testicular mass/CNS involvement).
TLH and < 5% blasts in bone marrow aspirate.
ANC > 1000/μL.
Platelets > 100,000/μL.
CRi required all criteria for CR except platelet count and/or ANC:
Platelets ≤ 100,000/μL and/or ANC is ≤ 1000/μL
PR required all criteria for CR except for bone marrow blasts:
bone marrow may contain ≥ 5% but less than 25% blast morphology
Time Frame
End of Induction (Cycle 2, Day 28)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
Adults with ALL in need of treatment
Key Exclusion Criteria:
Diagnosis of Burkitt's Leukemia, or lymphoid blast crisis of chronic myelogenous leukemia (CML)
History of myelodysplastic syndrome or solid organ transplantation
Prior allogeneic bone marrow progenitor cell transplant within 100 days or on active immunosuppression for graft versus host disease (GVHD) treatment or prophylaxis within 28 days prior to enrollment
Note: Other protocol defined Inclusion/ Exclusion criteria may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gilead Study Director
Organizational Affiliation
Gilead Sciences
Official's Role
Study Director
Facility Information:
Facility Name
City of Hope
City
Duarte
State/Province
California
ZIP/Postal Code
91010
Country
United States
Facility Name
UCLA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90095
Country
United States
Facility Name
UC Irvine Medical Center
City
Orange
State/Province
California
ZIP/Postal Code
92608
Country
United States
Facility Name
University of California San Diego (UCSD)
City
San Diego
State/Province
California
ZIP/Postal Code
92093
Country
United States
Facility Name
University of Chicago
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Hackensack University Medical Center
City
Hackensack
State/Province
New Jersey
ZIP/Postal Code
07601
Country
United States
Facility Name
Memorial Sloan-Kettering
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
The Ohio State University
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43210
Country
United States
Facility Name
Bon Secour St. Francis Hospital
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29601
Country
United States
Facility Name
University of WA
City
Seattle
State/Province
Washington
ZIP/Postal Code
98109
Country
United States
Facility Name
Princess Margaret
City
Toronto
State/Province
Ontario
Country
Canada
Facility Name
Medizinische Klinik mit Schwerpunkt Hepatologie & Gastroenterology
City
Berlin
ZIP/Postal Code
12200
Country
Germany
Facility Name
Medizinische Klinik und Poliklinik I
City
Wurzburg
Country
Germany
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Safety and Efficacy of Entospletinib With Vincristine and Dexamethasone in Adults With Relapsed or Refractory Acute Lymphoblastic Leukemia (ALL)
We'll reach out to this number within 24 hrs